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颈动脉超声的适应证——探查亚临床血管疾病及评估心血管疾病风险
动脉粥样硬化性血管病变在儿童时期就开始,在随后的几十年里悄然地发展 [1]。当动脉粥样硬化导致血流受限而引起缺血或由于斑块的破裂和侵蚀而导致血栓形成时,就会出现临床症状 [2]。首次发病即有可能是致命性的心肌梗死或高度致残性的脑卒中。虽然不是所有有动脉粥样硬化斑块的人都会发生临床心血管事件,但亚临床动脉粥样硬化的程度越严重,其发生心血管事件的风险也越大 [3-5]。高危无症状患者进行针对危险因素的强化治疗获益会最大,因此为了预防和减少心血管疾病的发病和死亡,及早甄别这一类人群已成为目前临床关注的焦点 [6,7]。
目前,那些高危患者主要是通过使用风险评分系统来发现的,比如SCORE或Framingham风险评分系统(FRS) [8,9]。然而它们对未来心血管事件的预测价值一般 [10]。于是有很多里程碑式的研究通过探查这些高危患者是否存在亚临床动脉粥样硬化来进一步提升对未来心血管事件的预测能力。这其中包括CT扫描冠状动脉钙化和颈动脉超声检查是否存在动脉粥样硬化。颈动脉超声的优势在于相对廉价、无创和没有电离辐射。于是在美国心脏协会和学院心脏病学会的指南中提出对心血管疾病中等风险程度的无症状患者进行心血管事件风险评估中,颈动脉内中膜厚度(CIMT)和冠状动脉钙化计分(CACS)是Ⅱa类推荐 [11]。在欧洲心血管预防指南中的推荐级别是Ⅱb [12]。
颈动脉超声检查内容和适用人群
颈动脉内中膜厚度(CIMT)和颈动脉斑块是评估颈动脉粥样硬化最常用的两大指标。CIMT是测量颈动脉壁最内侧两层的厚度。颈动脉斑块定义为局部的动脉壁增厚超过周围管壁的50%,或局部CIMT大于1.5mm并突入动脉管腔内 [13]。
对于中等心血管危险程度(FRS:6%~20%,无冠心病、周围动脉疾病、脑血管疾病、糖尿病或腹主动脉瘤)的患者,超声测量CIMT和探查颈动脉斑块对于评估心血管危险程度最有价值 [14]。
具有以下临床情况的患者也应当考虑颈动脉超声测量CIMT和探查颈动脉斑块:①一级亲属有早发心血管疾病的家族史(男性<55岁,女性<65岁);②年龄<60岁伴有单一危险因素且有严重病变者(比如:家族性遗传性血脂异常);③女性<60岁,有至少2个心血管危险因素 [14]。
CIMT对心血管疾病风险的预测价值
The Kuoppio缺血性心脏病研究是最早提出CIMT与未来冠脉事件的相关关系。该研究发现CIMT每增加0.1mm,心肌梗死的风险会增加11% [15]。随后,有几个大的临床研究,包括ARIC研究 [16]、CHS研究 [17]、CAPS研究 [18]、MDCS研究 [19]和Rotterdam研究 [20],均提出CIMT可以用来评估心血管疾病的风险。但有关CIMT能否在传统风险因素评分(FRS)的基础上提供附加预后信息的研究都没能得到阳性结果。
在动脉粥样硬化多种族研究研究中(Multi-ethnic Study of Atherosclerosis,MESA)发现,经过FRS调整后,颈总动脉IMT(CCA-IMT)不能预测冠心病或脑卒中的风险 [21]。CAPS研究显示即使CIMT对心血管事件有独立预测价值,但不能改善个体危险分层 [22]。Cooney等回顾性的研究发现颈动脉斑块对冠心病风险的预测价值要高于CIMT [23]。一项收纳了15篇相关文章的荟萃分析提出CIMT虽然与未来心血管事件相关,但把它加入到传统心血管疾病危险评估模型中后并不能进一步提升模型的预测价值 [24] 。但近期的一项研究提出采用专门的测量工具(cardiohealth station)后,CIMT对于基于传统风险因素评分为中危的患者具有再分层的价值,即从这些中危患者中能进一步找出更加高危的人群 [25]。有研究发现颈总动脉IMT(CCA-IMT)受收缩压影响更大 [26],对脑卒中有更好的预测价值 [27],而颈内动脉IMT(ICA-IMT)对动脉粥样硬化性心血管事件则有更好的预测价值 [28]。
CIMT与斑块对未来心肌梗死的预测价值比较
由于斑块的形成是动脉粥样硬化的表征,故此斑块的出现能预测未来心血管事件毫不稀奇。一项囊括了11项人群研究的荟萃分析显示与CIMT[包括颈总动脉、窦部和(或)颈内动脉]相比,颈动脉斑块对未来心梗的预测有更高的准确性和特异性 [29]。没有斑块者10年心血管事件的发生率明显低于CIMT正常者。一项荟萃分析发现单独测量颈动脉斑块比所有非斑块位置的IMT更能预测心血管事件 [30]。许多研究提示斑块比CIMT更能预测心血管事件。在ARIC研究中,当所有颈动脉节段的平均CIMT叠加传统风险因子(TRFs)和斑块后能显著增加对男性冠心病风险的预测价值 [31]。该研究中颈动脉斑块联合CIMT对中危患者的预测价值最大。三城市研究(Three-City Study)观察了5895例没有冠心病史的老年人(65~85岁),平均随访年限是5.4年。该研究发现颈动脉斑块的出现,而不是无斑块区CCA-IMT,是初发心脏事件的独立预测因子 [32]。传统风险因子叠加颈动脉斑块会显著改善心脏事件风险预测。随着斑块数量的增加,其心血管疾病的风险也显著增加。IMPROVE研究(Carotid Intima Media Thickness [IMT] and IMTProgression as Predictors of Vascular Events in a High Risk European Population)也观察到了类似的情况 [33]。该研究还发现在冠心病或心血管事件的再分层中,所有颈内动脉IMT最大值的平均值要比CCA远端IMT的平均值表现更好。
上述这些研究提示颈动脉斑块对动脉粥样硬化性心脏事件具有预测能力。斑块更易于在颈动脉窦部和颈内动脉内形成,这也许能解释为什么这些部位的IMT是心血管事件良好的预测因子,而单纯测量CCA-IMT或在没有斑块的位置测量的IMT对动脉粥样硬化性心脏病的预测价值不高。有研究发现,尽管颈动脉斑块对冠心病有良好的预测能力,但斑块与CIMT联合评价对于无症状糖尿病患者的冠状动脉疾病是更好的一线筛查工具 [34]。由于CCA-IMT增厚与脑卒中风险增加有关,联合FRS,IMT和斑块评估会提高对全部心血管事件的预测能力。
CIMT和斑块与危险因素的相关关系
英国区域性心脏研究发现CCA-IMT与颈动脉窦部IMT相关,但与两者分别相关的危险因素和动脉粥样硬化性疾病却不尽相同 [35]。CCA-IMT和与脑卒中有关的危险因素相关,而颈动脉窦部IMT及斑块和与缺血性心脏病有关的危险因素相关。IMT受遗传因素影响较大,而斑块看起来更多的受常见的冠心病危险因素影响 [36]。此外,斑块还与动脉的僵硬度等动脉粥样硬化指标有关,而IMT则不具有这种相关关系 [36]。尽管单中心研究已经提示类似超声这种影像结果会引致临床医生治疗模式的改变 [37,38],但仍需要随机临床研究来证实CIMT和斑块的评估是否能真正改善临床预后。故此2013年美国心血管危险评估指南并不推荐在临床实践中常规测量CIMT来预测心血管事件 [39]。
目前,由于缺乏IMT测量的统一标准,在临床实践中尚不推荐连续评估CIMT来监测动脉粥样硬化的进展或逆转 [14,40,41]。但在大型的临床研究中,由于有标准化的IMT操作流程,故此可以连续评估CIMT来监测动脉粥样硬化的进展或逆转 [36]。
IMT在年轻人中的应用价值
在年轻人中,CIMT提供了一个能反映动脉粥样硬化进程的可靠的和可测量的参数。因为在这个人群中动脉粥样硬化斑块或钙化都还没有形成,心脑血管事件可能要等到几十年后才能出现 [42]。
有研究已经发现,同健康的儿童相比,Ⅰ型糖尿病的肥胖儿童其平均CCA-IMT,颈动脉窦部IMT和ICA-IMT均显著增厚 [43]。年轻的吸烟者其CIMT尽管在正常范围,但要明显高于非吸烟者 [44]。川崎病儿童有冠状动脉瘤者,其CIMT逐年增加,而没有形成动脉瘤者,CIMT除了在疾病早期增加外,随后会逐年减低 [45]。Poyrazoglu等 [46]的研究发现有偏头疼的儿童其CIMT明显高于正常儿童,提出对这类患儿进行颈动脉超声检查以发现亚临床动脉粥样硬化。
故此,欧洲儿童心脏病协会心血管预防工作组提出儿童CIMT测量能提供有关血管损害的信息,并强调其在儿童心血管疾病预防中的预测价值。提出不同的测量方法会影响不同中心CIMT测量值的比较。统一测量方法会更利于多中心研究和比较 [47]。
结语
有关是否在危险分层中应用CIMT一直颇有争论,这与不同的CIMT研究中缺乏统一的方法学不无关系 [48]。无论是对于危险分层还是风险预测,在颈动脉窦部及颈内动脉测量的IMT比CCA-IMT更有价值。评价斑块负荷量比单纯描述斑块存在与否更能反映动脉粥样硬化程度和心血管疾病风险。但目前更倾向于定性评估,颈动脉斑块定量评价的可重复性还缺乏深入的研究。联合CIMT和斑块的评价比任何一种单独的评价更好。故此,临床推荐颈动脉超声仅适用于低-中等危险程度的患者,同时强调对结果的判读需结合所有心血管危险因素,不推荐将颈动脉超声用于临床随访监测 [49]。
(李为民 修春红)
参考文献
[1] McGill HC Jr, McMahan CA, Herderick EE, et al. Effects of coronary heart disease risk factors on atherosclerosis of selected regions of the aorta and right coronary artery: PDAY research group, Pathobiological Determinants of Atherosclerosis in Youth. Arterioscler Thromb Vasc Biol, 2000, 20: 836-845.
[2] Virmani R, Burke AP, Farb A, et al. Pathology of the vulnerable plaque. J Am Coll Cardiol, 2006, 47: C13-C18.
[3] Greenland P, Abrams J, Aurigemma GP, et al. Prevention conference V: beyond secondary prevention, identifying the high-risk patient for primary prevention, noninvasive tests of atherosclerotic burden, writing group Ⅲ. Circulation, 2000, 101: E16-E22.
[4] Taylor AJ, Merz CN, Udelson JE. 34th Bethesda conference: executive summary-can atherosclerosis imaging techniques improve the detection of patients at risk for ischemic heart disease. J Am Coll Cardiol, 2003, 41: 1860-1862.
[5] Greenland P, LaBree L, Azen SP, et al. Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individuals. JAMA, 2004, 291: 210-215.
[6] Graham I, Atar D, Borch-Johnsen K, et al. European guidelines on cardiovascular disease prevention in clinical practice: full text. Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts). Eur J Cardiovasc Prev Rehabil, 2007, 14 (Suppl 2): S1-S113.
[7] Perk J, De Backer G, Gohlke H, et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012): The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts)* Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J, 2012, 33 (13): 1635-1710.
[8] Conroy RM, Pyorala K, Fitzgerald AP, et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J, 2003, 24: 987-1003.
[9] McGorrian C, Leong T, D'Agostino R, et al. Risk estimation systems in clinical use: SCORE, Heart Score and the Framingham system // D'Agostino R, Graham I. Therapeutic Strategies in Cardiovascular Risk. Oxford, UK: Clinical Publishing, 2008.
[10] Batsis JA, Lopez-Jimenez F. Cardiovascular risk assessment--from individual risk prediction to estimation of global risk and change in risk in the population. BMC Med, 2010, 8: 29.
[11] Greenland P, Alpert JS, Beller GA, et al. ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol, 2010, 56: e50-e103.
[12] Perk J, De Backer G, Gohlke H, et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012): The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts)* Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J, 2012, 33 (13): 1635-1710.
[13] Roman MJ, Naqvi TZ, Gardin JM, et al. Clinical application of noninvasive vascular ultrasound in cardiovascular risk stratification: a report from the American Society of Echocardiography and the Society of Vascular Medicine and Biology. J Am Soc Echocardiogr, 2006, 19: 943-954.
[14] Stein JH, Korcarz CE, Hurst RT, et al. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Endorsed by the Society for Vascular Medicine. J Am Soc Echocardiogr, 2008, 21 (2): 93-111;quiz 189-190.
[15] Salonen JT, Salonen R. Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arterioscler Thromb, 1991, 11: 1245-1249.
[16] Chambless LE, Heiss G, Folsom AR, et al. Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC)Study, 1987-1993. Am J Epidemiol, 1997, 146: 483-494.
[17] O'Leary DH, Polak JF, Kronmal RA, et al. Distribution and correlates of sonographically detected carotid artery disease in the Cardiovascular Health Study. The CHS Collaborative Research Group. Stroke, 1992, 23: 1752-1760.
[18] Lorenz MW, Schaefer C, Steinmetz H, et al. Is carotid intima media thickness useful for individual prediction of cardiovascular risk? Ten-year results from the Carotid Atherosclerosis Progression Study (CAPS). Eur Heart J, 2010, 31: 2041-2048.
[19] Rosvall M, Janzon L, Berglund G, et al. Incident coronary events and case fatality in relation to common carotid intima-media thickness. J Intern Med, 2005, 257: 430-437.
[20] Bots ML, Hoes AW, Koudstaal PJ, et al. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation, 1997, 96: 1432-1437.
[21] Yeboah J, McClelland RL, Polonsky TS, et al. Comparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate risk individuals. JAMA, 2012, 308: 788-795.
[22] Lorenz MW, Schaefer C, Steinmetz H, et al. Is carotid intima media thickness useful for individual prediction of cardiovascular risk? Ten-year results from the Carotid Atherosclerosis Progression Study (CAPS). Eur Heart J, 2010, 31: 2041-2048.
[23] Simon A, Megnien JL, Chironi G. The value of carotid intima-media thickness for predicting cardiovascular risk. Arterioscler Thromb Vasc Biol, 2010, 30: 182-185.
[24] van den Oord SC, Sijbrands EJ, ten Kate GL, et al. Carotid intima-media thickness for cardiovascular risk assessment: systematic review and meta-analysis. Atherosclerosis, 2013, 228 (1): 1-11.
[25] Cooney M, Cooney MT, Maher V, et al. Improvement in the estimation of cardiovascular risk by carotid intima-medial thickness: A report from the Dublin Cardiohealth station study. Preventive Medicine Reports, 2015: 725-729.
[26] Ferreira JP, Girerd N, Bozec E, et al. Intima-Media Thickness Is Linearly and Continuously Associated With Systolic Blood Pressure in a Population-Based Cohort (STANISLAS Cohort Study).J Am Heart Assoc, 2016, 5 (6): e003529.
[27] Yeboah J, McClelland RL, Polonsky TS, et al. Comparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate-risk individuals. JAMA, 2012, 308: 788-795.
[28] Cao JJ, Arnold AM, Manolio TA, et al. Association of carotid artery intima-media thickness, plaques, and C-reactive protein with future cardiovascular disease and all-cause mortality: the Cardiovascular Health Study. Circulation, 2007, 116: 32-38.
[29] Inaba Y, Chen JA, Bergmann SR. Carotid plaque, compared with carotid intima-media thickness, more accurately predicts coronary artery disease events: a meta-analysis. Atherosclerosis, 2012, 220: 128-133.
[30] Spence JD, Yoichi Inaba, Jennifer A, et al. Carotid plaque measurement is superior to IMT: invited editorial comment on: carotid plaque, compared with carotid intimamedia thickness, more accurately predicts coronary artery disease events: a meta-analysis. Atherosclerosis, 2012, 220: 34-35.
[31] Nambi V, Chambless L, Folsom AR, et al. Carotid intima-media thickness and presence or absence of plaque improves prediction of coronary heart disease risk: the ARIC (Atherosclerosis Risk In Communities)study. J Am Coll Cardiol, 2010, 55: 1600-1607.
[32] Plichart M, Celermajer DS, Zureik M, et al. Carotid intima-media thickness in plaque-free site, carotid plaques and coronary heart disease risk prediction in older adults. The Three-City Study. Atherosclerosis, 2011, 219: 917-924.
[33] Baldassarre D, Hamsten A, Veglia F, et al. Measurements of carotid intima-media thickness and of interadventitia common carotid diameter improve prediction of cardiovascular events: results of the IMPROVE (Carotid Intima Media Thickness [IMT] and IMT-Progression as Predictors of Vascular Events in a High Risk European Population)study. J Am Coll Cardiol, 2012, 60: 1489-1499.
[34] Akazawa S, Tojikubo M, Nakano Y, et al. Usefulness of carotid plaque (sum and maximum of plaque thickness)in combination with intima-media thickness for the detection of coronary artery disease in asymptomatic patients with diabetes. J Diabetes Investig, 2016, 7 (3): 396-403.
[35] Ebrahim S, Papacosta O, Whincup P, et al. Carotid plaque, intima media thickness, cardiovascular risk factors, and prevalent cardiovascular disease in men and women: the British Regional Heart Study. Stroke, 1999, 30: 841-850.
[36] Naqvi TZ, Lee MS. Carotid intima-media thickness and plaque in cardiovascular risk assessment. J Am Coll Cardiol Img, 2014, 7: 1025-1238.
[37] Korcarz CE, DeCara JM, Hirsch AT, et al. Ultrasound detection of increased carotid intimamedia thickness and carotid plaque in an office practice setting: does it affect physician behavior or patient motivation. J Am Soc Echocardiogr, 2008, 21: 1156-1162.
[38] Marchesi F, Giacosa R, Reggiani V, et al. Morphological changes in the carotid artery intima after gastric bypass for morbid obesity. Obes Surg, 2016. [Epub ahead of print].
[39] Goff DC Jr., Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. J Am Coll Cardiol, 2014, 63 (25 PtB): 2935-2959.
[40] Lorenz MW, Price JF, Robertson C, et al. Carotid intima-media thickness progression and risk of vascular events in people with diabetes: results from the PROG-IMT collaboration.Diabetes Care, 2015, 38 (10): 1921-1929.
[41] Montalcini T, Romeo S, Fava A, et al. Carotid intima-media thickness: a target or a marker. Am J Ther, 2014, 21 (6): 535-539.
[42] Geerts CC, Bots ML, Grobbee DE, et al. Parental smoking and vascular damage in young adult offspring: is early life exposure critical? The atherosclerosis risk in young adults study. Arterioscler Thromb Vasc Biol, 2008, 28: 2296-2302.
[43] Urbina EM, Kimball TR, McCoy CE, et al. Youth with obesity and obesity-related type 2 diabetes mellitus demonstrate abnormalities in carotid structure and function. Circulation, 2009, 119: 2913-2919.
[44] Mozzini C, Casadei A, Roscia G, et al. Young smoker “ABCD” vascular assessment: a four-step ultrasound examination for detecting peripheral, extra and intra-cranial early arterial damage.BMC Cardiovasc Disord, 2016, 16 (1): 147.
[45] Haley J, Selamet Tierney ES. Patterns of carotid intima-media thickness progression in Kawasaki patients: a crystal ball for long-term vascular health. J Am Heart Assoc, 2016, 5 (7): e003778.
[46] Poyrazoglu HG, Vurdem UE, Arslan A, et al. Evaluation of carotid intima-media thickness in children with migraine: a marker of subclinical atherosclerosis. Neurol Sci, 2016. [Epub ahead of print].
[47] Dalla Pozza R, Ehringer-Schetitska D, Fritsch P, et al. Association for European Paediatric Cardiology Working Group Cardiovascular Prevention.Intima media thickness measurement in children: A statement from the Association for European Paediatric Cardiology (AEPC)Working Group on Cardiovascular Prevention endorsed by the Association for European Paediatric Cardiology. Atherosclerosis, 2015, 238 (2): 380-387.
[48] Ravani A, Werba JP, Frigerio B, et al.Assessment and relevance of carotid intima-media thickness (C-IMT)in primary and secondary cardiovascular prevention. Curr Pharm Des., 2015, 21 (9): 1164-1171.
[49] Ray A, Huisman MV, Rabelink TJ. Can and should carotid ultrasound be used in cardiovascular risk assessment?: the internist's perspective.Eur J Intern Med, 2015, 26 (2): 112-117.